Multidimensional mass spectrometry of serum and cellular lipids directly from biologic extracts

Abstract

A method for determination of at least one of the lipid species in a biological sample comprising subjecting the sample to lipid extraction to obtain a lipid extract and subjecting the resulting lipid extract to multidimensional electrospray ionization mass spectrometry using either precursor ion or neutral loss scanning (or both) of all naturally occurring aliphatic chains, lipid fragments and precursor ions leading to observed fragments to generate a multidimensional matrix whose contour densities provides structural and quantitative information directly without chromatography. A method for determination of lipid content and / or lipid molecular species composition and quantity directly from lipid extracts of a biological sample comprising subjecting said lipid extract to electrospray ionization multidimensional mass spectrometry by comparisons to standards and algorithms described herein.

Description

CROSS REFERENCE TO RELATED APPLICATION[0001]This application is a divisional of U.S. nonprovisional patent application Ser. No. 10 / 797,616, filed Mar. 10, 2004, which is a continuation in part of pending U.S. nonprovisional patent application Ser. No. 10 / 606,601, filed Jun. 26, 2003, which has issued as U.S. Pat. No. 7,306,952 and which claims priority to U.S. provisional patent application 60 / 391,711 filed Jun. 26, 2002, and claims the benefit of U.S. provisional patent application 60 / 458,733 filed Mar. 28, 2003 all of which are incorporated by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH & DEVELOPMENT[0002]This work was supported by grants from NIH including grants W / H P01 HL57278 / JDFI 996003, R02HL41250, RO1 AA11094, P41-RR00954, P60-DK20579, and P30-DK56341. The government has certain rights in the invention.FIELD OF THE INVENTION[0003]This invention relates generally to a method of analysis for lipids including triglycerides and other mentioned c...

AI Technical Summary

Benefits of technology

This approach provides a rapid, reliable method for analyzing triglycerides, enabling detailed molecular species profiling and risk assessment for conditions like coronary artery disease, stroke, and obesity, and facilitating the identification of effective lipid-modulating drugs.

Problems solved by technology

Additionally, such afflictions destroy or significantly reduce the quality of life even if not immediately fatal.

Although some studies have measured total TG molecular species content in multiple different disease states, a paucity of information on TG molecular species changes during pathophysiological alterations is available.

Previous attempts at direct TG quantitation by positive-ion electrospray ionization mass spectrometry (ESI / MS) were undesirably confounded by the presence of overlapping peaks from choline glycerophospholipids requiring chromatographic separation of lipid extracts prior to ESI / MS analyses.

Moreover, isobaric molecular species present in all biological tissues prevent determination of individual molecular species of triglycerides from molecular weight determinations alone.

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